Variants derived from ActRIIB and uses therefor

• US 10,259,861 B2
• Filed: 07/01/2016
• Issued: 04/16/2019
• Est. Priority Date: 02/02/2007
• Status: Active Grant

• Current Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Original Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Inventors: Knopf, John, Seehra, Jasbir, Kumar, Ravindra
• Primary Examiner(s): Kemmerer, Elizabeth C.
• Application Number:
  US15/201,031
• Publication Number:
  US 20170058016A1
• Time in Patent Office: 1,019 Days
• Field of Search: None
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07K 14/705 : Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/71 : for growth factors; for growth regulators
• CPC Class Codes: C07K 14/72 : for hormones for neuromediators C07K14/70571
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/70 : containing domain for protein-protein interaction

Abstract

In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of a tissue, such as bone, cartilage, muscle, fat, and/or neuronal tissue. The present invention also provides methods of screening compounds that modulate activity of an ActRIIB protein and/or an ActRIIB ligand. The compositions and methods provided herein are useful in treating diseases associated with abnormal activity of an ActRIIB protein and/or an ActRIIB ligand.

Claims

1. A variant ActRIIB protein consisting of the amino acid sequence of SEQ ID NO:

5.

2. The variant ActRIIB protein of claim 1, wherein the protein is a homodimer.

3. A pharmaceutical preparation comprising the variant ActRIIB protein of claim 1.

4. An isolated polynucleotide comprising a coding sequence for the variant ActRIIB protein of claim 1.

5. The isolated polynucleotide of claim 4, wherein the polynucleotide comprises the nucleic acid sequence of SEQ ID NO:

10.

6. A vector comprising the polynucleotide of claim 4.

7. A cell comprising the polynucleotide of claim 4, wherein the cell is not within a human.

8. A method of producing variant ActRIIB protein, the method comprising culturing the cell of claim 7 and expressing the variant ActRIIB protein.

9. The method of claim 8, wherein the cell is a CHO cell.

10. The method of claim 8, wherein the variant ActRIIB protein is expressed using a TPA leader sequence.

11. The method of claim 10, wherein the TPA leader sequence comprises the amino acid sequence of SEQ ID NO:

8.